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Aortic stenosis and the failing heart.

The combination of aortic stenosis and left-ventricular dysfunction is a challenging situation for the physician. Diagnosis of this condition requires a detailed evaluation to understand the etiology and reversibility of the ventricular dysfunction and to accurately determine the real severity of the stenosis. Whether the aortic stenosis the cause of the left ventricular failure or is an independent disease has significant diagnostic, prognostic and therapeutic implications. Dobutamine echocardiography provides critical information to determine the real severity and the left ventricle's potential to recover (contractile reserve). Attempts to delay the progression of the aortic stenosis with medical treatment have been limited, and valve replacement remains the hallmark of ultimate treatment. If surgery is inadvertently delayed, left ventricular systolic dysfunction will result in clinically evident congestive heart failure and this situation carries a very high short-term mortality. Aortic valve replacement in this setting improves the outcome, but perioperative mortality is high, and particularly when coronary revascularization is also needed, there is no ventricular contractile reserve and transvalvular gradients are low. Adequate timing of surgery is extremely important and increasingly more difficult. Management decisions should be tailored by the results of dobutamine echocardiography and made on a case-by-case basis.

Animals↗

Eplerenone, a selective aldosterone blocker, improves diastolic function in aged rats with small-to-moderate myocardial infarction.

BACKGROUND: The incidence of cardiovascular diseases increases rapidly with age, and the elderly suffer higher morbidity and mortality. Aldosterone blockers have shown benefits in patients with left ventricular (LV) dysfunction and heart failure after myocardial infarction (MI). However, aldosterone blockade efficacy has not been explored in aged animals with MI. Methods and results Small-to-moderate MI was induced by coronary artery ligation in 16-month old rats, divided into 3 groups: sham-operated (control, n = 9), MI (n = 9), and MI fed a diet containing eplerenone (120 mg/kg/day, MI+Eplerenone, n = 9) given 18 days postsurgery and up to sacrifice 3 months later. At sacrifice, untreated MI rats did not show overt systolic dysfunction but they had (1) echocardiographic evidences of impaired relaxation (increase of E wave deceleration time and of isovolumic relaxation time, decrease of peak E wave velocity), (2) hemodynamically impaired LV relaxation (LV -dP/dt from 7413 +/- 720 to 4956 +/- 475 mm Hg/s, P < .05), and (3) significant increase of collagen content in LV interstitium (from 4.27 +/- 0.23 to 5.34 +/- 0.24%, P < .01) and in aorta (from 19 +/- 1 to 24 +/- 2%, P < .05). Eplerenone normalized echocardiographic and hemodynamic evidences of diastolic dysfunction, as well as myocardial interstitial collagen and aortic fibrosis (all parameters statistically different from untreated MI). CONCLUSION: In aged rats with small to moderate MI, eplerenone normalized diastolic relaxation, possibly through a reduction of interstitial fibrosis.

Analysis of Variance↗

Preconditioning: myocardial function and energetics during coronary hypoperfusion and reperfusion.

BACKGROUND: Ischemic preconditioning (IP) is gaining more acceptance as a protective method in beating heart surgery. Yet it remains controversial whether preconditioning can attenuate myocardial dysfunction during reperfusion after severe coronary hypoperfusion. We examined this issue and also the issue of whether this protection is mediated by adenosine A1 receptors. METHODS: In isolated, blood-perfused rabbit hearts, the effects of IP (3 minutes of no flow ischemia and 8 minutes of reperfusion) during 30 minutes of coronary hypoperfusion and 60 minutes of reperfusion were investigated. In two groups (n = 8 each) with and without (control group) preconditioning, ventricular function was assessed by load-insensitive measures: slope of the end-systolic pressure-volume relation (Emax), slope of the stroke work/end-diastolic volume relation (Mw), and end-diastolic pressure-volume relation. External efficiency was calculated, and contractile efficiency was assessed using the reciprocal of the myocardial oxygen consumption-pressure-volume area relationship. To investigate the possible role of adenosine, the adenosine A1 receptor antagonist DPCPX (2.5 micromol/L) was administered before preconditioning in a third group (n = 7). RESULTS: The effects of hypoperfusion on systolic function, diastolic function (dP/dtmin, end-diastolic pressure-volume relation), external efficiency, and contractile efficiency were similar in both the IP and control groups. Lactate efflux was significantly reduced after preconditioning (p = 0.02). During reperfusion, recovery of systolic function and coronary flow were significantly improved in the IP group compared with controls: aortic flow, 85% versus 63% (p = 0.01); dP/dtmax, 91% versus 67% (p = 0.001); pressure-volume area, 97% versus 68% (p = 0.01); Emax, 74% versus 62% (p = 0.03); and Mw, 94% versus 84% (p = 0.04). Release of creatine kinase was reduced in the IP group, 9.6 +/- 1.3 U x 5 min(-1) x 100 g(-1) wet weight, versus controls, 12.7 +/- 2.7 U x 5 min(-1) x 100 g(-1) wet weight (p = 0.04). During reperfusion, contractile efficiency (p = 0.03) and external efficiency (p = 0.02) recovered better in preconditioned than in untreated hearts. Recovery was less pronounced in the DPCPX group compared with the IP group (p, not significant). CONCLUSIONS: The results, derived from load-insensitive measures, confirm that IP provides protection after episodes of severe hypoperfusion by attenuating systolic dysfunction without improving diastolic dysfunction and reduces the severity of anaerobic metabolism as well as ischemic injury. Contractile efficiency and external efficiency both indicate improved energetics after IP (oxygen utilization by the contractile apparatus). The protective effect, at least in part, is mediated by adenosine A1 receptors.

Animals↗

Left ventricular diastolic function in systemic sclerosis.

OBJECTIVE: To assess left ventricular diastolic function in patients with systemic sclerosis (SSc) and to verify if a "primary" diastolic dysfunction might exist. METHODS: In total 124 patients and 41 healthy subjects underwent complete echocardiographic examination. The following pulsed wave Doppler variables were evaluated: peak velocity during early filling (E), peak velocity during late atrial filling (A), E/A ratio, and early filling deceleration time. RESULTS: Seventy-seven patients (62.1%) had conditions potentially affecting left ventricular diastolic function (Group A) and 47 patients (37.9%) formed a homogeneous group without cardiac involvement or other causes of abnormal diastolic function (i.e., systemic and/or pulmonary hypertension, ventricular hypertrophy, pericardial disease, systolic dysfunction, valvular heart disease, coronary artery disease) (Group B). The entire SSc population and Group A showed significant differences in the Doppler variables of diastolic function compared to the control group. No significant differences were found between Group B and controls. CONCLUSION: In patients with SSc, left ventricular diastolic dysfunction was found only in patients with conditions potentially affecting left ventricular diastolic function. In patients without conditions potentially affecting left ventricular diastolic function no differences were seen in comparison with controls. SSc does not seem to cause "primary" diastolic abnormalities.

Adult↗

Doppler echocardiographic evaluation of left ventricular diastolic filling in isolated valvular aortic stenosis.

Doppler echocardiography was used to study left ventricular (LV) diastolic filling in 49 adults with isolated aortic stenosis (AS), selected from 155 consecutive patients with AS by excluding coexisting mitral disease (n = 41) and/or significant aortic regurgitation (n = 80). There were no differences between patients with AS and age-matched normal subjects for early diastolic filling (E) velocity (68 +/- 17 vs 67 +/- 13 cm/s), late diastolic filling (A) velocity (79 +/- 25 vs 67 +/- 21 cm/s), E/A ratio (1.00 +/- 0.78 vs 1.06 +/- 0.32) or early diastolic deceleration slope (264 +/- 151 vs 319 +/- 137 cm/s2, differences not significant for all). There was no correlation between any LV filling parameter and AS severity, but late diastolic filling velocity was higher in patients with AS who had LV hypertrophy (n = 33) vs those who did not (n = 16) (86 +/- 23 vs 65 +/- 26 cm/s, p less than 0.01). In the patients with AS and systolic dysfunction (LV ejection fraction less than 50%) (n = 6), early diastolic filling velocity was higher (88 +/- 20 vs 65 +/- 15 cm/s, p less than 0.01), late diastolic filling velocity lower (53 +/- 23 vs 83 +/- 23 cm/s, p less than 0.01), E/A ratio higher (2.20 +/- 1.80 vs 0.84 +/- 0.28, p less than 0.01), deceleration slope steeper (439 +/- 230 vs 240 +/- 121 cm/s2, p = 0.02) and LV end-diastolic pressure higher (23 +/- 9 vs 10 +/- 6 mm Hg, p less than 0.01) than in patients with AS and normal systolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Myocardial microvascular abnormalities observed by intravenous myocardial contrast echocardiography in patients with hypertrophic cardiomyopathy.

We tested the hypothesis that myocardial microvascular abnormalities occur and are influenced by clinical features in 30 patients with hypertrophic cardiomyopathy (HC) using intravenous myocardial contrast echocardiography. Patients with HC were subdivided into 3 groups: nonobstructive HC (n = 12), obstructive HC (n = 10), or HC with systolic dysfunction and heart failure (n = 8). In patients with nonobstructive HC and obstructive HC, subendocardial peak myocardial contrast intensity at the mid-septal area was significantly decreased and the transmyocardial difference of peak myocardial contrast intensity between subendocardial and periendocardial regions at the mid-septal area was significantly related to regional wall thickness. Reduced peak myocardial contrast intensities at the mid-septal subendocardial and periendocardial regions were observed in patients with HC and heart failure. Our study indicates that subendocardial microvascular abnormalities during end-systole may be associated with severity of regional myocardial hypertrophy in patients with nonobstructive HC and obstructive HC. In addition, progressive microvascular damage may occur in patients with HC and heart failure.

Aged↗

Significance of inducible nitric oxide synthase in acute myocarditis caused by Trypanosoma cruzi (Tulahuen strain).

Chagas' disease, caused by Trypanosoma cruzi, is associated with myocarditis and expression of myocardial cytokines and inducible nitric oxide synthase (NOS2). To assess the functional significance of NOS2 in murine Chagas' disease, we infected NOS2 knockout (NOS2(-/-)) and C57BL/6x129sv (wild type) mice with the Tulahuen strain of T. cruzi. Serial transthoracic echocardiography was performed to assess the progression of left and right ventricular dysfunction in infected mice. Uninfected wild type and NOS2(-/-) mice served as controls. At day 10 post-infection (p.i.), infected wild type mice had larger left ventricular end-diastolic diameter (2.52+/-0.14-vs-2.11+/-0.06 mm, P<0.02) and right ventricle (0.6+/-0.2-vs-0 visual grade, P<0.02) as compared with uninfected wild type mice. At day 19 p.i., compared with uninfected controls, infected wild type mice had larger left ventricular end-diastolic diameter (3.30+/-0.29-vs-2.11+/-0.07 mm), left ventricular end-systolic diameter (1.86+/-0.29-vs-0.88+/-0.05 mm), right ventricle (1.6+/-0.2-vs-0 visual grade), lower heart rate (413+/-27-vs-557+/-25 beats per min), left ventricular relative wall thickness (0.44+/-0.05-vs-0.64+/-0.03) and fractional shortening (45+/-4-vs-57+/-2%) [P<0.05 for all]. In contrast, no differences in left ventricular end-diastolic diameter or fractional shortening were noted among infected and uninfected NOS2(-/-) mice at day 19 p.i. Compared with uninfected controls, infected NOS2(-/-) mice had significantly lower heart rate (272+/-23-vs-512+/-31 beats per min, P<0.01) and larger right ventricle (0.6+/-0.2-vs-0, P<0.05 visual grade). The magnitude of right ventricular dilation in NOS2(-/-) mice was less than that observed in infected wild type mice. At necropsy, the heart weight was greater (129+/-16-vs-109+/-7 mg, P=0.02) and myocardial inflammation more severe in infected wild type compared with infected NOS2(-/-) mice. Myocardial interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha, and interferon-gamma were induced in all infected mice. These data indicate that nitric oxide derived from NOS2 plays an important role in the development and progression of ventricular dilation and systolic dysfunction in acute murine chagasic myocarditis caused by infection with the Tulahuen strain.

Animals↗

Do patients with suspected heart failure and preserved left ventricular systolic function suffer from "diastolic heart failure" or from misdiagnosis? A prospective descriptive study.

OBJECTIVES: To characterise the clinical features of patients with suspected heart failure but preserved left ventricular systolic function to determine if they have other potential causes for their symptoms rather than being diagnosed with "diastolic heart failure." DESIGN: Prospective descriptive study. SETTING: Outpatient based direct access echocardiography service. PARTICIPANTS: 159 consecutive patients with suspected heart failure referred by general practitioners. MAIN OUTCOME MEASURES: Symptoms (including shortness of breath, ankle oedema, and paroxysmal nocturnal dyspnoea) and history of coronary heart disease and chronic pulmonary disease. Transthoracic echocardiography, body mass index, pulmonary function tests, and electrocardiography. RESULTS: 109 of 159 participants had suspected heart failure in the absence of left ventricular systolic dysfunction, valvular heart disease, or atrial fibrillation. Of these 109, 40 were either obese or very obese, 54 had a reduction in forced expiratory volume in 1 second to </=70%, and 97 had a peak expiratory flow rate </=70% of normal. Thirty one patients had a history of angina, 12 had had a myocardial infarction, and seven had undergone a coronary artery bypass graft. Only seven patients lacked a recognised explanation for their symptoms. CONCLUSIONS: For most patients with a diagnosis of heart failure but preserved left ventricular systolic function there is an alternative explanation for their symptoms-for example, obesity, lung disease, and myocardial ischaemia-and the diagnosis of diastolic heart failure is rarely needed. These alternative diagnoses should be rigorously sought and managed accordingly.

Angina Pectoris↗

Attenuation of cardiac dysfunction by a PPAR-alpha agonist is associated with down-regulation of redox-regulated transcription factors.

Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a key regulator of lipid and glucose metabolism and is implicated in inflammation. We investigated the effects of the PPAR-alpha activator fenofibrate on, as well as the role of redox-regulated transcription factors, in the development of left ventricular (LV) hypertrophy and heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed a high-salt diet and treated with either fenofibrate (30 or 50 mg/kg per day) or vehicle from 7 weeks of age. Fenofibrate inhibited the development of compensated hypertensive LV hypertrophy, attenuated the LV relaxation abnormality and systolic dysfunction, and improved the survival rate in DS rats. It also prevented a decrease in the ratio of reduced to oxidized glutathione and inhibited up-regulation of the DNA binding activities of the redox-regulated transcription factors NF-kappaB, AP-1, Egr-1, SP1, and Ets-1 induced in the left ventricle by the high-salt diet. Expression of target genes for these transcription factors, including those for adhesion molecules (VCAM-1, ICAM-1), cytokines (MCP-1), growth factors (TGF-beta, PDGF-B), and osteopontin, was also increased by the high-salt diet in a manner sensitive to treatment with fenofibrate. Furthermore, the infiltration of macrophages and T lymphocytes into the left ventricle and the increase in the plasma concentration of C-reactive protein were inhibited by fenofibrate. The PPAR-alpha activator fenofibrate thus attenuated the progression of heart failure and improved the survival rate in this rat model. These effects were associated with inhibition of the inflammatory response and of activation of redox-regulated transcription factors in the left ventricle.

Animals↗

Combination of B-type natriuretic peptide levels and non-invasive hemodynamic parameters in diagnosing congestive heart failure in the emergency department.

This study aimed to assess whether the combination of a B-type natriuretic peptide (BNP) level with various noninvasive hemodynamic parameters can help physicians more quickly and accurately diagnose congestive heart failure and determine the type of left ventricular dysfunction present in patients presenting to the emergency department with dyspnea. Subjects were 98 men (aged 64.57+/-1.23 years) that presented to the VA San Diego Healthcare System. Hemodynamic parameters were measured using impedance cardiography, and BNP levels were quantified using a rapid immunoassay. All patients with a BNP <100 pg/mL (n=37) had no evidence of congestive heart failure 97% of the time. In those with a BNP >100 pg/mL (601+/-55 pg/mL; n=61), a cardiac index of 2.6 L/min/m2 is 65% sensitive and 88% specific in determining systolic dysfunction. In patients with a BNP >100 pg/mL, a multivariate model consisting of noninvasive hemodynamic measurements was able to predict cardiac deaths, readmissions, and emergency department visits within 90 days with 83% accuracy. The authors conclude that, in patients presenting to an emergency department with dyspnea, the addition of impedance cardiography measurements to BNP level measurements will more effectively diagnose congestive heart failure and determine both the type of heart dysfunction and the severity of illness.

Aged↗

[The mechanisms of diastolic dysfunction and their assessment by a Doppler method].

The Doppler method makes possible to reveal the relaxation disturbances and the increased left ventricular (LV) stiffness-pathophysiologic mechanisms of diastolic myocardial dysfunction (DMD), exerting opposite influence on the correlation of transmitral flow peaks. The decrease of the "diastolic reserve" in the patients with lung congestion is useful to diagnose DMD. But the type of LV filling, when the relative role of early diastole is decreased and of the late diastole-increased, cannot itself be recognized as pathologic. From the other side, the normal transmitral flow graphics doesn't allow to exclude DMD completely. The interpretation of Doppler parameters must take into consideration other factors influencing the LV diastolic filling: preload, systolic dysfunction and mitral regurgitation.

Diastole↗

Beta-blocker therapy in patients with heart failure in the urban setting: moving beyond clinical trials.

BACKGROUND: Despite their known benefits, beta-blockers (BBL) are not yet widely prescribed for heart failure, especially in the primary care setting. We wanted to identify patient characteristics that could guide primary care physicians in deciding whether they or a cardiologist should initiate BBL. A second objective was to determine the tolerability of BBL in clinical practice. METHODS: A retrospective chart review was conducted on a consecutive series of 551 patients with systolic dysfunction referred to a heart failure clinic in an urban public hospital. Patient responses to BBL were stratified into three categories: favorable (improvement of left ventricular ejection fraction by serial echocardiography), unfavorable (development of decompensated heart failure), or neither. Tolerability of BBL was assessed by the need to permanently discontinue BBL. RESULTS: Of 551 patients, 363 (66%) tolerated BBL. Among patients who had BBL initiated in the clinic, 48 had a favorable response, 34 had an unfavorable response, and 57 had neither a favorable or unfavorable response, as defined. A lower systolic blood pressure and higher diuretic dose were associated with development of decompensated heart failure as compared to improvement of ejection fraction. CONCLUSIONS: A majority of patients with heart failure in an urban public hospital can tolerate BBL. Easily measurable characteristics such as lower systolic blood pressure and higher diuretic dose may assist primary care physicians in triaging patients for referral to cardiologists for beta-blocker initiation.

Adrenergic beta-Antagonists↗

Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion.

BACKGROUND: Glucose-insulin-potassium infusions are beneficial in uncomplicated patients with acute myocardial infarction (AMI) but are of unproven efficacy in AMI with left ventricular (LV) dysfunction because of volume requirements associated with glucose infusion. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with both insulinotropic and insulinomimetic properties that stimulate glucose uptake without the requirements for concomitant glucose infusion. METHODS AND RESULTS: We investigated the safety and efficacy of a 72-hour infusion of GLP-1 (1.5 pmol/kg per minute) added to background therapy in 10 patients with AMI and LV ejection fraction (EF) <40% after successful primary angioplasty compared with 11 control patients. Echocardiograms were obtained after reperfusion and after the completion of the GLP-1 infusion. Baseline demographics and background therapy were similar, and both groups had severe LV dysfunction at baseline (LVEF=29+/-2%). GLP-1 significantly improved LVEF (from 29+/-2% to 39+/-2%, P<0.01), global wall motion score indexes (1.94+/-0.11-->1.63+/-0.09, P<0.01), and regional wall motion score indexes (2.53+/-0.08-->2.02+/-0.11, P<0.01) compared with control subjects. The benefits of GLP-1 were independent of AMI location or history of diabetes. GLP-1 was well tolerated, with only transient gastrointestinal effects. CONCLUSIONS: When added to standard therapy, GLP-1 infusion improved regional and global LV function in patients with AMI and severe systolic dysfunction after successful primary angioplasty.

Adult↗

Valvular heart disease: aortic regurgitation.

Aortic regurgitation (AR) is characterized by diastolic reflux of blood from the aorta into the left ventricle (LV). Acute AR typically causes severe pulmonary edema and hypotension and is a surgical emergency. Chronic severe AR causes combined LV volume and pressure overload. It is accompanied by systolic hypertension and wide pulse pressure, which account for peripheral physical findings, such as bounding pulses. The afterload excess caused by systolic hypertension leads to progressive LV dilation and systolic dysfunction. The most important diagnostic test for AR is echocardiography. It provides the ability to determine the cause of AR and to assess the severity of AR and its effect on LV size, function, and hemodynamics. Many patients with chronic severe AR may remain clinically compensated for years with normal LV function and no symptoms. These patients do not require surgery but can be followed carefully for the onset of symptoms or LV dilation/dysfunction. Surgery should be considered before the LV ejection fraction falls below 55% or the LV end-systolic [corrected] dimension reaches 55 mm. Symptomatic patients should undergo surgery unless there are excessive comorbidities or other contraindications. The primary role of medical therapy with vasodilators is to delay the need for surgery in asymptomatic patients with normal LV function or to treat patients in whom surgery is not an option. The goal of vasodilator therapy is to achieve a significant decrease in systolic arterial pressure. Future therapies may focus on molecular mechanisms to prevent adverse LV remodeling and fibrosis.

Aortic Valve Insufficiency↗

[Stability of NT-ProBNP in patients with systolic heart failure].

Natriuretic peptides are extremely useful in the diagnosis and prognosis of patients with heart failure. However, it is not clear whether their values are stable. We carried out a prospective study of 30 consecutive ambulatory patients (mean age, 62.6 [12.2] years) with stable systolic heart failure, as determined by the 6-minute walk test, who were in New York Heart Association class II or III and who had a left ventricular ejection fraction <30% (mean ejection fraction, 24.2% [6.68%]). At baseline, the mean N-terminal pro-brain natriuretic peptide (NT-proBNP) level and the mean distance walked in 6 minutes were 2237.3 pg/mL and 348.26 m, respectively. At 3-month follow-up, the corresponding values were 2096.2 pg/mL and 372.05 m, respectively. No significant difference was observed in NT-proBNP level or in distance walked in 6 minutes between baseline and 3 months (P=.8). Overall, there was a good correlation (r=0.94; P< .001) between the plasma NT-proBNP level at baseline and at 3 months in patients with stable chronic heart failure due to systolic dysfunction in New York Heart Association class II or III.

Data Interpretation, Statistical↗

Rapid histological changes in endomyocardial biopsy specimens after myocarditis.

The course and response to treatment in acute lymphocytic myocarditis are conventionally monitored by endomyocardial biopsy performed every 3-12 weeks. A patient with a short history (five days) of acute myopericarditis of unknown aetiology presented in cardiogenic shock with evidence of severe systolic dysfunction on the echocardiogram. The initial biopsy specimen showed histologically unequivocal myocarditis. Repeat endomyocardial biopsy after four days of treatment with steroids and azathioprine showed substantial histological improvement, a reduction in cellular infiltrate and myocardial necrosis, and interstitial fibrosis. Serial biopsies at 2 weeks and then 1, 2, 4, 5, 8, and 14 months after the initial biopsy showed progressive clearing of cellular infiltrate, increasing interstitial fibrosis, and compensatory myocyte hypertrophy by 4 months. At 14 months scattered lymphocytes persisted but myocyte abnormalities had resolved completely. The patient remained symptom free and systolic function was normal during this recovery period. Early endomyocardial biopsy (within one week of diagnosis) may yield useful histological information on the response to treatment in patients with myocarditis. It may not be necessary to wait the customary 3-4 weeks to repeat the biopsy. This case shows the chronology of histological changes and emphasises that a return to normal myocardial function may precede resolution of the histological abnormalities, which may persist in part or may resolve totally after the acute episode.

Acute Disease↗

A continued role for beta-blocker therapy in heart failure.

The number of patients with newly diagnosed heart failure continues to grow worldwide, to some extent reflecting the increase in survival after acute coronary syndromes and the aging of the population. The search for new and effective therapies for this condition remains a priority in the 21st century. The use of beta-blockers is now well established in the clinical context of mild and moderate systolic heart failure. The effects of beta-blockade on mortality are additive to those with angiotensin-converting enzyme inhibitor therapy. Recently completed, large, randomized trials provided strong evidence for the use of beta-blockers in severe (NYHA functional class IV) heart failure and in asymptomatic patients with left ventricular systolic dysfunction and recent myocardial infarction. Obviously, patient selection still remains the key to the safe use of beta-blockers in patients with heart failure. Further data from clinical trials have emerged to support similar benefits in terms of mortality and morbidity, a good safety record, and tolerability in patients at extremes of age (children and adults >70 years of age) and in specific clinical circumstances (including diabetes, chronic obstructive airways disease, renal failure, and atrial fibrillation). Recent use of beta-blockers with vasodilatory properties in patients with heart failure and preserved systolic function (so-called diastolic heart failure) appears promising but will require large-scale, long-term trials prior to widespread clinical use.

Adrenergic beta-Antagonists↗

Mitral annular calcification in CAPD patients with a low degree of hyperparathyroidism. An analysis of other possible risk factors.

Chronic renal failure has been suggested as a risk factor for mitral annular calcification (MAC), a degenerative process of the mitral annulus. The objective of the present study was to define MAC risk factors at the start of dialysis and 'de-novo' appearance after medium- or long-term CAPD, in a non-selected population (135 patients) with a low degree of secondary hyperparathyroidism. Echocardiographic studies were performed at the beginning of CAPD and every 1-1.5 years thereafter. Diagnosis of MAC was established by M mode and 2-D study. Seventeen of 135 patients studied at the start of dialysis showed MAC. Patients who showed MAC were older and presented a higher mean systolic blood pressure. The other anthropometric/demographic parameters did not show statistically significant differences. MAC thickness: mean 6.21 +/- 3.65 mm (range 3-17.2 mm). The posterior annulus was universally affected and in four patients the anterior annulus was involved. Seventeen of 76 patients included in the follow-up study developed MAC. No significant differences for demography, except age, with MAC patients being older, were found. Mean time on CAPD until de-novo MAC diagnosis was 49.7 +/- 26.9 months. MAC thickness: mean 4.97 +/- 1.6 mm (range 3-8.42 mm). The posterior annulus was affected in all patients except for one and in four patients the anterior annulus was involved. The most remarkable echocardiographic feature is the almost constant association of MAC with left atrial dilatation (LAD). The last one does not seem a consequence of mitral insufficiency, or systolic dysfunction. Left ventricular hypertrophy was universally found, with no different intensities for patients with or without MAC. In conclusion, a high incidence of mitral annular calcification has been found in CAPD patients. Our data do not confirm the role of classical invoked risk factors. Blood CaP product under 75, a moderate to mild degree of hyperparathyroidism and/or hypertension with left ventricular hypertrophy do not seem to be isolated risk factors during the CAPD period. Length of time on CAPD, for unknown reasons, seems to favour the appearance of MAC. At starting dialysis, high systolic blood pressure and left ventricular hypertrophy seem to be related to MAC. Diabetes appears to represent an additional risk factor. Further research on mitral annular calcification pathogenesis and its consequences is urgently required.

Calcinosis↗